The Roles of Topoisomerases in Transcriptional Regulation

Torsional stress from DNA supercoiling is receiving renewed attention as a driving force for chromosome folding and the establishment of gene activity states. Transcription is a major source of DNA supercoiling, while topoisomerases relax supercoils and solve topological problems that arise during DNA replication, transcription, and chromosome segregation. Recent technological advancements have allowed for the mapping of how torsional stress distributes within the genome and distinguishing between occupancy of topoisomerases on chromatin and sites where they are catalytically engaged. Coupling these innovations to assessments of 3D chromosome conformation and nascent transcription at high resolution have provided a new understanding of the relationships between supercoiling and topoisomerase activity. Here, we summarize the insights obtained from these recent studies and discuss how the interplay between transcription, supercoiling, and topoisomerases shapes cellular gene activity states.